The overall goal of this Program Project is to design, construct, manufacture and test a therapeutic vaccine for use in persons infected with human immunodeficiency virus type 1 (HIV). The vaccine vectors are derived from Venezuelan equine encephalitis virus (VEE) and have proven safe and immunogenic in rodent and primate model systems. In this Project, AlphaVax, Inc. will be responsible for cGMP manufacture of the VEE replicon particle (VRP) vaccine, GLP testing of the vaccine product, and submission of the IND application for the Program Project. AlphaVax has developed an initial GMP-compliant manufacturing process for production of Phase I quantities of an HIV clade C vaccine utilizing VRP and is scheduled to submit an IND for a Phase I trial of this prophylactic vaccine in December 2001. This body of process development work represents a substantial advantage for the therapeutic vaccine envisioned in this application. The manufacturing process and testing protocols for the proposed therapeutic HIV clade B vaccine will be virtually identical to the clade C product, and many of these processes can be included in the regulatory documentation for the proposed clade B therapeutic vaccine by reference to the clade C regulatory submissions. AlphaVax will prepare the plasmid DNAs, produce clinical supplies under cGMP, characterize the product through in-process and release testing, prepare the final formulated product, conduct GLP pivotal toxicology studies and prepare the IND submission.